Comparison of surgical outcomes and prognosis between wedge resection and simple Segmentectomy for GGO diameter between 2cm and 3cm in non-small cell lung cancer: A multicenter and propensity score matching analysis

Chia sẻ: _ _ | Ngày: | Loại File: PDF | Số trang:11

Thêm vào BST

Báo xấu

29
lượt xem 1
download

Download Vui lòng tải xuống để xem tài liệu đầy đủ

As segmentectomy had become commonly used for Non-Small Cell Lung Cancer (NSCLC) treatment, which had the advantages of radical operation, however, it remains controversial owing to procedural complexity and risk of increased complications compared with wedge resection.

Chủ đề:

Bình luận(0) Đăng nhập để gửi bình luận!

Lưu

Nội dung Text: Comparison of surgical outcomes and prognosis between wedge resection and simple Segmentectomy for GGO diameter between 2cm and 3cm in non-small cell lung cancer: A multicenter and propensity score matching analysis

Zhou et al. BMC Cancer (2022) 22:71 https://doi.org/10.1186/s12885-021-09129-0 RESEARCH Open Access Comparison of surgical outcomes and prognosis between wedge resection and simple Segmentectomy for GGO diameter between 2 cm and 3 cm in non-small cell lung cancer: a multicenter and propensity score matching analysis Yaodong Zhou1*†, Tao Yu1†, Yixin Zhang2, Liqiang Qian3 and Qing Xia4* Abstract Background: As segmentectomy had become commonly used for Non-Small Cell Lung Cancer (NSCLC) treatment, which had the advantages of radical operation, however, it remains controversial owing to procedural complexity and risk of increased complications compared with wedge resection. We evaluated operative and postoperative outcomes of simple segmentectomy compared to wedge resection in ground-glass opacity (GGO) diameter between 2 cm and 3 cm NSCLC. Methods: We retrospectively reviewed 1600 clinical GGO diameter between 2 cm and 3 cm NSCLC patients who received simple segmentectomy and wedge resection between Jan 2011 and Jan 2015. Participants were matched 1:1 on their propensity score for two groups. Clinic-pathologic, operative, and postoperative results of two groups were compared. Results: After using propensity score methods to create a matched cohort of participants with simple segmentec- tomy group similar to that wedge resection, there were no significant differences detected in tumor size, margin dis- tance, histology, age, sex, preoperative comorbidities and preoperative pulmonary function. Overall complications in simple segmentectomy group were more than wedge resection group (21% vs 3%, p = 0.03). Median operative time (110.6 vs. 71.2 min; p = 0.01) and prolonged air leakage (12% vs. 3%; p = 0.02) was significantly longer in the simple segmentectomy group. There was no difference in recurrence free survival (RFS) and overall survival (OS) of 5-years between simple segmentectomy group and wedge resection group. Postoperative pulmonary function in simple segmentectomy group recovered more slowly than wedge resection group. *Correspondence: yaodongzhou@shca.org.cn; yaodongzhou@shca.org.cn † Yaodong Zhou and Tao Yu are first co-authors with equal contribution. 1 Yaodong Zhou, Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong‑An Road, Shanghai 200032, People’s Republic of China 4 Department of Neonate, Children’s Hospital of Fudan University, Shanghai 201102, China Full list of author information is available at the end of the article © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Zhou et al. BMC Cancer (2022) 22:71 Page 2 of 11 Conclusion: Wedge resection may have comparable efficacy as simple segmentectomy for GGO diameter between 2 cm and 3 cm NSCLC, but lead to less complications, less surgical procedure and faster recovery of pulmonary function. Keywords: NSCLC, Segmentectomy, Wedge resection, Ground-glass opacity, Propensity score matching Background The debate often centers on the surgical procedure Over the last few decades, pulmonary lobectomy with required for ground-glass nodules 1 to 2 cm in size. Few systemic meditational lymphadenectomy has been cho- studies have explored the clinical outcomes of simple sen as the standard surgical therapy for NSCLC, which segmentectomy vs wedge resection in GGO diameter found that sublobar resection was associated with infe- between 2 cm and 3 cm NSCLC. We evaluated pre-oper- rior overall survival and high recurrence chance com- ative condition, operative, postoperative outcomes, pared to pulmonary lobectomy [1]. After that, sublobar prognosis and variations of pulmonary function in those resection is just performed only for patients unable to patients who underwent simple segmentectomy versus tolerate lobectomy. However, in recent ten years, the wedge resection. widespread of the lung cancer CT-screening programs together with progression in imaging, have lead to a Patients and methods large number of GGO diagnosed [2]. Many researches Study population have reported that sublobar resection for small size This retrospective study comprised of patients(n = 1600) tumors of stage I NSCLC can yield similar outcomes to with clinical GGO diameter between 2 cm and 3 cm those patients undergoing lobectomy [3, 4]. Therefore, NSCLC who underwent lung operation at the Shang- pulmonary segmentectomy probably could become the hai Ninth People’s Hospital Affiliated to Shanghai Jiao- standard treatment choice for NSCLC with early stage tong University, Shanghai Chest Hospital and Children’s recently, which is selected more frequently [5]. However, hospital of Fudan University between January 2011 and wedge resection, still as one of sublobar resection type, January 2015. The present study was approved by the has been criticized for its marginal recurrence and short Research Ethics Committee of Shanghai Jiaotong Uni- of thoroughness without lymph node dissection, which versity (Shanghai, People’s Republic of China), and writ- affects its clinical value [4]. ten informed operation-consent was obtained from all Segmentectomy could be further subdivided into patients. Patient inclusion criteria were acceptable to simple segmentectomy and complex segmentectomy, tolerate pulmonary lobectomy as evaluated by cardi- according to surgical procedure. Complex segmentec- orespiratory fitness tests. All the operations were purely tomy needed to create artificial intersegmental planes, simple segmentectomy or wedge resection. We excluded with more complex procedures, such as resection of the patients in whom the surgeon mixed the operation, such Right Superior (RS) (1 + 3), RS3, Left Inferior (LI) 9, and as lobectomy + wedge resection or segmentectomy + LI (9 + 10) segments, etc. Simple segmentectomy, usu- wedge resection. ally called “classic segmentectomy”, easy to create linear intersegmental plane, was more regular in operation, Propensity score methods such as RS 2, Right Inferior(RL)6, RL(7 + 8 + 9 + 10), Propensity score matching was used to reduce these LS(1 + 2 + 3) segments, left lingular segment, LI 6 and selection biases when estimating the association of differ- LI(7 + 8 + 9 + 10). Though simple segmentectomy do ent sublobar resection with complications and prognosis. not need complex procedure, surgeons still often isolate To calculate the propensity score, we used logistic regres- and divide suitable segmental vein, artery, bronchus, and sion to obtain the predicted probability of exposure (i.e. in some cases separate into lung parenchyma especially tumor size, margin distance, tumor site, surgical types). suffering the poor intersegmental plane. We focus on The propensity scores were obtained based on the most simple segements because they are the classic and most accurate and clinically relevant model including the base- widely used surgical procedures for segements. However, line variables: age, sex, preoperative cardiopulmonary higher complications rates, such as prolonged air leakage, function, smoking status, surgical types, histology, and longer stay in hospital, and length of chest tube drainage tumor site. Using this model, we could create propensity are concerned [6]. Wedge-shaped resection of the lung score weights for all participants to guarantee there were has the advantages of simpler procedure, less operation no missing values. time and controllable margin. Especially with preopera- Patients with simple segmentectomy group tive CT-guiding puncture location, it will become easier. were matched 1-to-1 without replacement using a
Zhou et al. BMC Cancer (2022) 22:71 Page 3 of 11 varying-width caliper-matching algorithm (5-to-1 digit relapse mainly refers to local lymph node relapse, both matching). The propensity scores were then checked to of which are the focus of our follow-up. All the patients ensure they were balanced across the simple segmen- underwent pulmonary function test from pre-operation tectomy and wedge resection groups. The balance in to postoperative at 3, 6 and 12 months. covariates was assessed before and after matching using standardized differences. Importantly, standardized dif- Statistical analysis ferences of 0.2, 0.5 and 0.8 were deemed to represent tiny, The collected data are presented as numbers or median medium and huge differences, respectively [7]. (interquartile range) or mean value. The statistical method used for comparing RFS and OS is log-rank. Dif- Preoperative evaluation ferences in the multifarious variables between simple seg- All the patients received careful preoperative staging with mentectomy and wedge resection groups were assessed CT, cardio-pulmonary function testing within 4 weeks of by Fisher’s test or the Mann-Whitney U test, in which the surgical procedure. The emission computed tomog- measurement data were used by Paired t-test and count raphy (ECT), Positron Emission Tomography-Com- data were used by McNemar’s test. Prognostic factors for puted Tomography (PET-CT), brain magnetic resonance survival were identified using a multivariate Cox propor- imaging and tracheabronchoscopy was dependent by tional hazards model. Pulmonary function changes after the surgeon who judged it whether or not necessary. simple segmentectomy or wedge section group were Tumor stage was determined according to the size of compared by repeated-measures analysis of variance tumor, nodes, and metastasis classification of malignant and time-dependent variations in the forced vital capac- tumors on the basis of 8th edition [8]. All the diameter of ity (FVC), forced expiratory volume in 1 s (FEV1.0), pre- ground grass opacity nodule (GGO) or solid nodules was dicted diffusing capacity of the lung for carbon monoxide between 2 and 3 cm. Patients with solid component size (DLCO%) and peak expiratory flow (PEF) were evaluated. 2 cm or over were excluded. All tests were two-sided and a p value less than or equal to 0.05 was set as statistical significance. All the data was Surgical procedure analyzed statistically using SPSS 19.0 (IBM, Armonk, NY, In general, the choice between wedge resection and seg- USA). mental resection is a decision made by each surgeon based on expert consensus or guidelines combined with Results his own judgment. Surgical Procedure mainly involved Overall, 1600 patients who had undergone lung surgery anatomic pulmonary segmentectomy or resection of were assessed for eligibility (Fig. 1). After excluding 140 wedge to guarantee acceptable resection margin, and to who did not provide consent, 120 due to incomplete fol- isolate hilar, segmental, and excise or sample mediastinal lowing up, and 330 benign tumors, our study involved lymph nodes to confirm N0 treatment. All the patients 1010 participants. Then, we excluded 60 because of in the wedge resection group mostly need to receive incomplete clinical data, 310 who do not receive sublobar CT-guided needle localization. All the operations were resection and 130 mixed different operations. There were performed by VATS with two incisions or three inci- 510 patients left for propensity score matching (Sup- sions. Surgeons were allowed to mark and divide the plementary table), which resulted in simple segmentec- intersegmental plane, using argon beam, electrocautery, tomy group (n = 100) versus the wedge resection group or segmental stapling to secure adequate surgical mar- (n = 100) forming 1:1 matching (Fig. 1, Table 1). Signifi- gin and the inflation–deflation line. After resection, the cantly different with full cohort, the matching reduce surgeon should confirm the result of pathology and sur- the selection bias and make the variables similar, such as gical margin again. If the surgical margin was not satis- age, gender, tumor size, margin distance, smoking sta- fied, additional wedge resection was required to extend tus, tumor site, histology, preoperative cardiopulmonary the distance. function and so on (Table 1). Follow‑up Clinicopathologic data in patients Perioperative condition data and intra-operative data In the two groups, adenocarcinoma accounts for the were collected from the hospital medical records, anes- highest percentage of pathology (total n = 180, 90%), thesia, and operating room records for each patient. including adenocarcinoma in situ (AIS), microinva- Postoperative complications were summarized using the sive adenocarcinoma (MIA), and invasive adenocar- Clavien–Dindo classification [9]. Relapse patterns mainly cinoma (IA), followed by squamous cell carcinoma include local relapse, regional relapse and distant relapse. (total n = 13, 6.5%, Table 2). There were no significant Local relapse mainly refers to margin relapse, region differences in clinic-pathologic data, including age,
Zhou et al. BMC Cancer (2022) 22:71 Page 4 of 11 Fig. 1 Flow chart of study enrolment and exclusion sex, number of solid nodules, mixed GGO (mGGO), Postoperative outcomes pure GGO (pGGO), preoperative pulmonary function In the postoperative outcome analysis, no deaths testing, pathology, or tumor size between two groups. occurred in perioperative period after segmentectomy Varieties of comorbidities, such as coronary artery dis- and wedge resection. The median hospital stay and ease, chronic obstructive pulmonary disease (COPD) median length of drainage in simple segmentectomy and diabetes mellitus were similar in both groups group was longer than wedge resection group (5.2 vs 3.1, (Table 2). p = 0.043; 3.4 vs 2.2, p = 0.043, respectively, Table 4). The average hospitalization expenses in simple segmentec- tomy group was more than wedge resection group (5020$ Surgical outcomes vs 3900$, p = 0.035). Overall complications occurred in In our study, simple segmentectomy included resec- the simple segmentectomy group were more than wedge tion of the RS2, RS6, LS(1 + 2 + 3), LS6, or lingual resection group (21% vs 3%, p = 0.031, Table 4). segment (Table 3). Median operative time was obvi- ously longer for the simple segmentectomy group ver- sus the wedge resection group (110.6 min vs 71.2 min, Prognosis of 5‑years p = 0.002, Table 4). However, estimated blood loss was All the patients were followed up for 5 years after not significantly different (150 ml vs. 130 mL, p = 0.07). operation. The median follow-up time was 62 months. Median surgical margins were similar (19.5 mm vs The time of reexamination of chest CT was 6, 18, 36, 22.4 mm, p = 0.7). No postoperative marginal recur- 48, 60 and 84 months after surgery, respectively. The rence occurred in either group. Mean number of dis- 5-year RFS and OS in simple segmentectomy group sected lymph nodes during simple segmentectomy was 93.1 and 91.9%, and in wedge resection group group was more than wedge resection group (4.0 VS was 96 and 95.7% before propensity score matching 1.5 = 0.003). (Supplementary figure). Importantly, after propensity
Zhou et al. BMC Cancer (2022) 22:71 Page 5 of 11 Table 1 Baseline characteristics of study participants according to different operation group status in unmatched and matched cohorts Variables Full cohort After propensity score matching Simple Wedge Standardized Simple Wedge Standardized segmentectomy resection Differencea segmentectomy resection differencea group group group group (n = 160) (n = 350) (n = 100) (n = 100) General data Age 55.4(13.5) 62.9(16.2) 0.28 57.2(14.1) 57.7(14.2) 0.002 Male 95(59.3%) 192(54.8%) 0.91 58(58%) 53(53%) 0.015 Tumor size(cm) 2.92(0.2) 2.64(0.17) 0.48 2.73(0.19) 2.71(0.19) 0.011 Solid component size 1.54(0.14) 1.92(0.19) 0.37 1.78(0.17) 1.82(0.18) 0.013 Smoking status Ever 77(48.1%) 198(56.5%) −0.39 47(47%) 49(49%) 0.003 Margin(mm) 13.2(4.2) 25.7(5.6) −0.66 19.5(3.6) 22.4(4.1) 0.002 Median operative time(min) 121.7(25.3) 62.9(14.3) 0.53 110.6(19.5) 71.2(17.9) 0.013 Blood loss (ml) 210(45.1) 120(21.7) 0.77 150(26.8) 130(24.2) 0.001 Dissected lymph nodes(n) 6(0.57) 2.5(0.29) 0.55 4(0.34) 1.5(0.31) 0.006 Tumor Site RUL 33(20.6%) 81(23.1%) 0.456 21(21%) 19(19%) 0.01 RML 0 14(4%) 0.65 0 3(3%) 0.018 RLL 31(19.3%) 97(27.7%) −0.541 23(23%) 26(26%) −0.009 LUL 48(30%) 69(19.7%) −0.42 37(37%) 33(33%) 0.01 LLL 48(30%) 89(25.4%) −0.47 19(19%) 19(19%) 0 Histology Adenocarcinoma 142(88.7%) 287(82%) −0.41 91(91%) 89(89%) 0.01 AIS 46(28.8%) 98(28%) −0.33 29(29%) 26(26%) 0.05 MIA 57(35.6%) 123(35.1%) −0.51 32(32%) 34(34%) 0.04 IA 39(24.3%) 66(18.9%) 0.21 30(30%) 29(29%) −0.012 Pulmonary function (%) 58.6%(4.9) 53.7%(3.7) 0.35 57.3%(4.5) 54.2%(3.8) 0.05 Poor pulmonary functionb 34(21.2%) 81(23.1%) −0.44 21(21%) 24(24%) 0.02 Ejection fraction (%) 67.1%(5.8) 60.2%(5.1) 0.38 64.6%(5.6) 61.7%(5.1) 0.041 Poor ejection fractionc 22(13.8%) 31(8.9%) 0.31 16(16%) 13(13%) 0.023 Data are expressed as mean (SD) or number (%). a Standardized differences of 0.2, 0.5 and 0.8 were deemed to represent tiny, medium and huge differences, respectively. These differences do not denote statistical significance b Poor pulmonary function was defined as an FEV1/FVC ratio of
Zhou et al. BMC Cancer (2022) 22:71 Page 6 of 11 Table 2 Patient and tumor characteristics of simple Table 3 Tumor locations of simple segmentectomy group and segmentectomy and wedge resection wedge resection group Variables simple wedge resection p value Locations simple segmentectomy wedge segmentectomy n = 100 n = 100 resection n = 100 n = 100 Age (years) 0.14 Right upper 19 > 60 65 62 S2 21 ≤ 60 35 38 S3 0 Sex 0.22 Right middle 0 3 Male 58 53 Right lower 26 Female 42 47 S6 20 Comorbidities 0.08 S(7 + 8 + 9 + 10) 3 Coronary artery 13 15 Left upper 33 disease S(1 + 2 + 3) 25 Diabetes mellitus 17 20 lingular segment 12 COPD 17 14 Left lower 19 Tumor size (mm) 26.7 25.9 0.43 S6 17 CTR 0.78 0.75 0.69 S(7 + 8 + 9 + 10) 2 Clinical Stage cTisN0 25 24 0.39 cT1miN0 36 34 0.67 cT1aN0 16 17 0.54 pulmonary functions test and there is no censoring. Dur- cT1bN0 14 14 0.78 ing the postoperative period, we observed both the two mGGO 45 43 0.54 groups showed a different course of lung function in the pGGO 55 57 0.66 test of FVC, FEV1.0, DLCO% and PEF after postoperative Pulmonary function a 57.3% 54.2% 0.21 3 months, 6 months and 12 months. However, patients in Ejection fraction 64.6% 61.7% 0.15 the wedge resection group showed up better recovery of Histology pulmonary function compared with simple segmentec- Adenocarcinoma 91(91%) 89(89%) 0.09 tomy group (p = 0.04, p = 0.032, p = 0.03, 0.025, respec- AIS 29 26 tively; Fig. 3). MIA 32 34 IA 30 29 Discussion Squamous cell 6(6%) 7(7%) 0.07 In recent decades, there has been so much research carcinoma focusing on short and long term prognosis and com- Others 3(3%) 4(4%) 0.33 plications between pulmonary lobectomy, segmentec- Pathologic stage tomy and wedge resection [5, 10]. Controversies still pTisN0 29 26 0.34 exist on the most valuable choice. Mounts of litera- pT1miN0 32 34 0.43 ture in the world has proved the use of sublobar resec- pT1aN0 12 14 0.22 tion for patients with small, peripheral NSCLC [2, PT1bN0 18 15 0.26 11]. Okada et al. reported the segmentectomy patients Visceral pleural inva- 1 1 reached almost the same 5-year survival rate (87.1% vs sion 87.7%), which is almost equivalent to lobectomy group Lymphovascular inva- 3 2 sion in patients with T1N0 tumors [12]. In addition, overall a recurrence rates were also similar after segmentectomy FEV1/FVC ratio COPD Chronic obstructive pulmonary disease, GGO Ground-glass opacity, FEV1 (17.6%) and lobectomy (16.7%) [4]. Therefore, sublobar Forced expiratory volume in 1 s, FVC Forced vital capacity, CTR Consolidation resection had become a more conventional option for tumor ratio those early stage NSCLC patients. Sublobar resection could be subdivided into segmen- tectomy and wedge resection. According to surgical Postoperative changes of pulmonary functions process, segmentectomy included simple and complex Finally, we compared the pulmonary functional varia- segmentectomy. In our study, we just choose simple tions in the simple segmentectomy group and wedge segmentectomy or we call it “classical segmentectomy”. resection (Fig. 3). All the 200 patients received the Actually, simple segmentectomy is more conventional
Zhou et al. BMC Cancer (2022) 22:71 Page 7 of 11 Table 4 Operative and postoperative data of simple segmentectomy and wedge resection Variables simple segmentectomy wedge resection p value n = 100 n = 100 Operative data time (min) 110.6 71.2 0.002 blood loss (ml) 150 130 0.07 margin (mm) 19.5 22.4 0.07 dissected lymph nodes (n) 4 1.5 0.003 staple1 (n) 4.2 4.7 Postoperative data stay in hospital (day) 5.2 3.1 0.043 hospitalization expenses ($) 5020 3900 0.035 drainage (day) 3.4 2.2 0.04 air leakage (> 7 day) 12 3 0.02 Postoperative complications overall 21(21%) 3(3%) 0.031 pulmonary infection 7 1 atelectasis 8 2 chylothorax 5 0 bleeding 1 0 Relapse patterns 0.22 local relapse 0 0 region relapse 4 3 distant relapse 2 2 1 Numbers of staple for complete the operation and common used in many centers. However, because of margins seems to be more than sufficient. These results the worry about lymph node and margin relapse, wedge highlight the favorable biology (and of course less aggres- resection was taken to perform seriously and deliber- siveness) of this kind of tumor in the Asian population, ately. Some studies reported that wedge resection suf- which could not be reproducible for the rest of the world fered more incidences of local recurrence and lower OS (Europe or America). than segmentectomy [13, 14]. It restricted the application Several researches reported that affirming satisfac- of wedge resection. However, we explored the pre-oper- tory surgical margins was strikingly significant to effec- ative, operative and postoperative outcomes of patients tively prevent margin relapse, even though the resection undergoing simple segmentectomy and wedge resec- margin has a negative pathological result [17]. It is still tion, including morbidity, complications, surgical margin, uncertain what the margin is enough in the operation lymph nodes, prognosis and recovery of pulmonary func- to avoid relapse again. Generally speaking, 20 mm mar- tion between two groups. No patient in both groups died gin in an inflated lung and 15 mm in a deflated lung were during the perioperative period. Compared with simple believed to be safe and suitable [18]. In addition, one pro- segmentectomy group, wedge resection group entirely spective and multicenter study has reported that margin showed less operative time (71.2 min vs 110.6 min, distance greater than the tumor diameter was considered p = 0.002), drainage time (2.2 vs 3.4 days, p = 0.04), stay optimal for avoiding margin relapse [19]. In the study of in hospital (3.1 days vs 5.2 days, p = 0.043) and hospital Tsutani et al., postoperative recurrence occurred in 36 of expense (3900$ vs 5020$, p = 0.035). Moreover, there 195 patients (18.5%) undergoing wedge resection and 14 were similar 5-years OS (Fig. 2) in both groups. These of 262 patients (5.3%) undergoing segmentectomy. Can- complications are less and OS are higher than in previ- cer control was better in segmentectomy than in wedge ous reports after segmentectomy or wedge resection [15, resection [20]. Suzuki et al. reported that Median patho- 16]. The wedge resection group showed remarkably pri- logical surgical margin was 15 mm (0–55) and the 5-year ority on simple segmentectomy group in our study. From relapse-free survival was 99.7% (90% confidence inter- our study, to stage GGO diameter between 1 cm and val, 98.3–99.9). Sublobar resection with enough surgical 2 cm, segmentectomy is overkill. A wedge with negative margin offered sufficient local control and relapse-free
Zhou et al. BMC Cancer (2022) 22:71 Page 8 of 11 Fig. 2 The 5-year RFS and OS in simple segmentectomy group was 94 and 95%, and in wedge resection group was 95 and 96%. There was no difference on the RFS and OS between simple segmentectomy group and wedge resection group survival for lung cancer clinically resectable N0 staged by Enough dissection of lymph nodes is significant not computed tomography with 3 or fewer peripheral lesions only to secure effect of radical excision but also to pre- 2.0 cm or less amenable to sublobar resection and with vent tumor metastasis and recurrence. One study rec- a consolidation tumor ratio of 0.25 or less [21]. In our ommended that at least six dissection nodes to ensure research, the mean surgical margin in patients undergo- proper TNM classification, but it was the requirement ing operation was strictly at least 19.5 mm, which was of lobectomy [22]. To those stage IA patients, it does not longer than Suzuki et al’ report (Table 4). Actually, no need so many [23, 24]. He et al. reported that sublobar patient in the two groups suffered relapse at the surgical resection patients with ≥3 evaluated lymph nodes are margin, which is different from Tsutani et al’ study. The associated with better overall survival and lung cancer- reason may still be that our margins are longer. Wedge specific survival [25]. Similarly, Dezube et al. defined has probably been used for very peripheral lesion and lymph node sampling minimums in early stage NSCLC, segmentectomy is suitable for deeper lesion not accessi- retrospectively analyzing the National Cancer Database ble for a wedge. Even if it is difficult to examine in the (NCDB) queried 2004–2014 for surgically treated clini- study, segmentectomy should remain the standard to cal stage I/II NSCLC. These differences were not sta- obtain large surgical margin. In our study, wedge resec- tistically significant until the number of 4 removed LN tion actually had better margins. The reason may be that (respectively 3 for wedge-resections). For segmentec- the surgeon may prefer to remove a larger portion of the tomies, median survival was not statistically associated lung during the operation of wedge resection. with number of LN sampled. Based on NCDB data, LN
Zhou et al. BMC Cancer (2022) 22:71 Page 9 of 11 Fig. 3 The pulmonary function changes in simple segmentectomy group and wedge resection group. A-D There were forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), predicted diffusing capacity of the lung of carbon monoxide percentage (%DLCO) and peak expiratory flow (PEF) preoperatively at 3, 6 and 12 months postoperatively in patients undergoing simple segmentectomy group and wedge resection group sampling for lung cancer resections is recommended FVC, FEV1.0, DLCO% and PEF (Fig. 3). Isolating and [26]. In our study, the median number of dissected splitting pulmonary segments, evening cutting into lung lymph nodes during operation in simple segmentec- parenchyma, still had some effect on pulmonary func- tomy was 4 and in the wedge resection group, there is tion, especially the recovery of pulmonary function. only 1.5. The incidence of lymph nodes metastasis was 3 and 4%, respectively, which exist no difference (p = 0.08). Limitations The number of dissected lymph nodes doesn’t seem to The present study had several limitations. First, it was a be important for AIS or MIA. However, frozen section retrospective study and results are derived from 3 centers should be standard to rule out invasive adenocarcinoma, only in the Shanghai area. The limited data might have because complete lymph node dissection is still manda- introduced bias. Second, because we use a propensity tory in this subgroup and wedge with one lymph node is score matching method, the analyzed patients of segmen- not the appropriate treatment. There is a relevant issue, tectomy group may be biased toward the similar charac- as second primary lung cancer is often seen in the follow- teristics of wide-wedge resection group after matching. up of these patients. Baig et al. reported that anatomic Third, multiple regression analysis may have confounding resection has superior long-term survival compared with bias. wedge resection for second primary lung cancer after prior lobectomy. Significant improvement in survival was Conclusions observed with wedge resection for second primary lung In summary, wedge resection may have comparable cancer when adequate lymph node dissection was per- efficacy as simple segmentectomy for GGO diameter formed [27]. between 2 cm and 3 cm in NSCLC, but lead to less com- Another concern about postoperative pulmonary func- plications, less surgical procedure and faster recovery of tion changes in two groups. We could find postoperative pulmonary function. Moreover, securing operation mar- pulmonary function in segmentectomy group recover gins and lymph nodes of dissection could be performed more slowly than wedge resection group according to as effective measures whatever segmentectomy or wedge
Zhou et al. BMC Cancer (2022) 22:71 Page 10 of 11 resection. Further investigations, larger samples and 2. Goya T, Asamura H, Yoshimura H, Kato H, Shimokata K, Tsuchiya R, et al. Prognosis of 6644 resected non-small cell lung cancers in Japan: a longer time following-up will be needed. Japanese lung cancer registry study. Lung Cancer. 2005;50:227–34. 3. Gu C, Wang R, Pan X, Huang Q, Zhang Y, Yang J, et al. Sublobar resec- Supplementary Information tion versus lobectomy in patients aged ≤35 years with stage IA non-small cell lung cancer: a SEER database analysis. J Cancer Res Clin The online version contains supplementary material available at https://doi. Oncol. 2017;143:2375–82. org/10.1186/s12885-021-09129-0. 4. Tsutani Y, Miyata Y, Nakayama H, Okumura S, Adachi S, Yoshimura M, et al. Appropriate sublobar resection choice for ground glass opacity- Additional file 1: Supplementary figure. The 5-year RFS and OS in sim- dominant clinical stage IA lung adenocarcinoma: wedge resection or ple segmentectomy group was 93.1 and 91.9%, and in wedge resection segmentectomy. Chest. 2014;145:66–71. group was 96 and 95.7% before propensity score matching. 5. Berfield KS, Wood DE. Sublobar resection for stage IA non-small cell lung cancer. J Thorac Dis. 2017;9(Suppl 3):S208–10. Additional file 2: Supplementary table. All the patients and tumor 6. Hattori A, Matsunaga T, Takamochi K, Oh S, Suzuki K. Locoregional characteristics of simple segmentectomy and wedge resection before recurrence after segmentectomy for clinical-T1aN0M0 radiologi- propensity score matching. cally solid non-small-cell lung carcinoma. Eur J Cardiothorac Surg. 2017;51:518–25. 7. Austin PC. Balance diagnostics for comparing the distribution of Acknowledgements baseline covariates between treatment groups in propensity-score We thank Haiquan Chen MD, for his help in editing this manuscript. matched samples. Stat Med. 2009;28:3083–107. 8. Rami-Porta R, Bolejack V, Crowley J, Ball D, Kim J, Gustavo L, et al. The Authors’ contributions IASLC Lung Cancer Staging Project: Proposals for the Revisions of the T Conception & Design of the study: YZ, QX and YXZ; Data collection: YZ, TY and Descriptors in the Forthcoming Eighth Edition of the TNM Classifica- LQ; Interpretation of data: YZ and YXZ; Drafting of the manuscript: YZ; Revised tion for Lung Cancer. J Thorac Oncol. 2015;10:1515–22. work and provided important intellectual content: YZ and QX. All authors have 9. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, read and approved the manuscript. et al. The Clavien-Dindo classification of surgical complications: five- year experience. Ann Surg. 2009;250:187–96. Funding 10. Altorki N, Lee B. Commentary: lobectomy or sublobar resection for This study was supported in part by the national natural science foundation of early lung cancer: one small step for surgeons, one giant step for China (81902310, 81802270). patients. J Thorac Cardiovasc Surg. 2019;158:909–10. 11. Stiles BM, Mao J, Harrison S, Lee B, Port JL, Sedrakyan A, et al. Extent Availability of data and materials of lymphadenectomy is associated with oncological efficacy of The datasets analysed during the current study are available from the cor- sublobar resection for lung cancer ≤2 cm. J Thorac Cardiovasc Surg. responding author on reasonable request. 2019;157:2454–65. 12. Okada M, Sakamoto T, Nishio W, Uchino K, Tsubota N. Characteris- Declarations tics and prognosis of patients after esection of non-small cell lung carcinoma measuring 2 cm or less in greatest dimension. Cancer. Ethics approval and consent to participate 2003;988:535–41. The present study was approved by the Research Ethics Committee of 13. Zhang Y, Sun Y, Wang R, Ye T, Zhang Y, Chen H. Meta-analysis of lobec- Shanghai Jiaotong University (Shanghai, People’s Republic of China), and tomy, segmentectomy,and wedge resection for stage I non-small cell written informed operation-consent was obtained from all patients. All the lung cancer. J Surg Oncol. 2015;111:334–40. experiment protocol for involving human data was in accordance with the 14. Zhao M, Lu T, Huang Y, Yin J, Jiang T, Li M, et al. Survival and long-term guidelines of national/international/institutional or Declaration of Helsinki in cause-specific mortality associated with stage IA lung adenocarcinoma the manuscript. after wedge resection vs. Segmentectomy: a population-based propen- sity score matching and competing risk analysis. Front Oncol. 2019;9:593. Consent for publication https://doi.org/10.3389/fonc.2019.00593. eCollection 2019. Not applicable. 15. Atkins BZ, Harpole DH Jr, Mangum JH, Toloza EM, D’Amico TA, Burfeind WR Jr. Pulmonary segmentectomy by thoracotomy or thoracoscopy: Competing interests reduced hospital length of stay with a minimally-invasive approach. Ann The authors declare that they have no competing interests. Thorac Surg. 2007;84:1107–13. 16. McKenna RJ, Houck W, Fuller CB. Video-assisted thoracic surgery lobec- Author details tomy: experience with 1,100 cases. Ann Thorac Surg. 2006;81:421–6. 1 Yaodong Zhou, Department of Thoracic Surgery, Fudan University Shanghai 17. Sato M, Kobayashi M, Kojima F, Tanaka F, Yanagiya M, Kosaka S, et al. Effect Cancer Center, 270 Dong‑An Road, Shanghai 200032, People’s Republic of virtual-assisted lung mapping in acquisition of surgical margins in of China. 2 Department of Plastic and Reconstructive Surgery, Shanghai Ninth sublobar lung resection. J Thorac Cardiovasc Surg. 2018;156:1691–1701. People’s Hospital affiliated to Shanghai Jiaotong University, Shanghai 200011, e5. China. 3 Department of Thoracic Surgery, Shanghai Chest Hospital, Shang- 18. Kadota K, Nitadori J-I, Sima CS, Ujiie H, Rizk NP, Jones DR, et al. Tumor hai 200030, China. 4 Department of Neonate, Children’s Hospital of Fudan spread through air spaces is an important pattern of invasion and University, Shanghai 201102, China. impacts the frequency and location of recurrences after limited resection for small stage I lung adenocarcinomas. J Thorac Oncol. 2015;10:806–14. Received: 19 June 2021 Accepted: 20 December 2021 19. Sawabata N, Ohta M, Matsumura A, Nakagawa K, Hirano H, Maeda H, et al. Optimal distance of malignant negative margin in excision of non- small cell lung cancer: a multicenter prospective study. Ann Thorac Surg. 2004;77:415–20. 20. Tsutani Y, Handa Y, Shimada Y, Ito H, Ikeda N, Nakayama H, et al. Compari- References son of cancer control between segmentectomy and wedge resection 1. Shapiro M, Weiser TS, Wisnivesky JP, Chin C, Arustamyan M, Swanson SJ. in patients with clinical stage IA non-small cell lung cancer. J Thorac Thoracoscopic segmentectomy compares favorably with thoracoscopic Cardiovasc Surg. 2020;S0022-5223:32833–6. lobectomy for patientswith small stage I lung cancer. J Thorac Cardiovasc 21. Suzuki K, Watanabe S-I, Wakabayashi M, Saji H, Aokage K, Moriya Surg. 2009;137:1388–93. Y, et al. A single-arm study of sublobar resection for ground-glass
Zhou et al. BMC Cancer (2022) 22:71 Page 11 of 11 opacity dominant peripheral lung cancer. J Thorac Cardiovasc Surg. 2020;S0022-5223:33043–9. 22. Lardinois D, De Leyn P, Van Schil P, Porta RR, Waller D, Passlick B, et al. ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer. Eur J Cardiothorac Surg. 2006;30:787–92. 23. Tsutani Y, Miyata Y, Nakayama H, Okumura S, Adachi S, Yoshimura M, et al. Sublobar resection for lung adenocarcinoma meeting node-negative criteria on preoperative imaging. Ann Thorac Surg. 2014;97:1701–7. 24. Cox ML, Yang CJ, Speicher PJ, Anderson KL, Fitch ZW, Gu L, et al. The role of extent of surgical resection and lymph node assessment for clinical stage I pulmonary Lepidic adenocarcinoma: an analysis of 1991 patients. J Thorac Oncol. 2017;12:689–96. 25. He Z, Li Z, Song X, Weibing W, Zhu Q, Wang J, et al. Prognostic signifi- cance of lymph node count removed at sublobar resection in pathologic stage IA non-small-cell lung Cancer: a population-based analysis. Clin Lung Cancer. 2020;S1525-7304:30295–3. 26. Dezube AR, Mazzola E, Bravo-Iñiguez CE, De León LE, Rochefort MM, Bueno R, et al. Analysis of lymph node sampling minimums in early stage non-small-cell lung Cancer. Semin Thorac Cardiovasc Surg. 2020;S1043-0679:30399–3. 27. Baig MZ, Razi SS, Stroever S, Weber JF, Connery CP, Bhora FY. Anatomic resection has superior long-term survival compared with wedge resec- tion for second primary lung cancer after prior lobectomy. Eur J Cardio- thorac Surg. 2021;59(5):1014-20. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in pub- lished maps and institutional affiliations. Ready to submit your research ? Choose BMC and benefit from: • fast, convenient online submission • thorough peer review by experienced researchers in your field • rapid publication on acceptance • support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations • maximum visibility for your research: over 100M website views per year At BMC, research is always in progress. Learn more biomedcentral.com/submissions